Publications

Cannabis is one of the most commonly used substances in the world. However, its effects on human cognition are not yet fully understood. Although the cerebellum has the highest density of cannabinoid receptor type 1 (CB1R) in the human brain, literature on how cannabis use affects cerebellar-dependent learning is sparse. This study examined the effect of chronic cannabis use on sensorimotor adaptation, a cerebellar-mediated task, which has been suggested to depend on endocannabinoid signaling.Chronic cannabis users (n = 27) with no psychiatric comorbidities and healthy, cannabis-naïve controls (n = 25) were evaluated using a visuomotor rotation task. Cannabis users were re-tested after 1 month of abstinence (n = 13) to assess whether initial differences in performance would persist after cessation of use.Cannabis users showed lower adaptation rates compared to controls at the first time point. However, this difference in performance did not persist when participants were retested after one month of abstinence (n = 13). Healthy controls showed attenuated implicit learning in the late phase of the adaptation during re-exposure, which was not present in cannabis users. This explains the lack of between group differences in the second time point and suggests a potential alteration of synaptic plasticity required for cerebellar learning in cannabis users.Overall, our results suggest that chronic cannabis users show alterations in sensorimotor adaptation, likely due to a saturation of the endocannabinoid system after chronic cannabis use.Copyright © 2022 Elsevier Ltd. All rights reserved.

JTD Keywords: Addiction, Cannabis, Cerebellum, Endocannabinoid system, Visuomotor adaptation

Chronic use of cannabis leads to both motor deficits and the downregulation of CB1 receptors (CB1R) in the cerebellum. In turn, cerebellar damage is often related to impairments in motor learning and control. Further, a recent motor learning task that measures cerebellar-dependent adaptation has been shown to distinguish well between healthy subjects and chronic cannabis users. Thus, the deteriorating effects of chronic cannabis use in motor performance point to cerebellar adaptation as a key process to explain such deficits. We review the literature relating chronic cannabis use, the endocannabinoid system in the cerebellum, and different forms of cerebellar-dependent motor learning, to suggest that CB1R downregulation leads to a generalized underestimation and misprocessing of the sensory errors driving synaptic updates in the cerebellar cortex. Further, we test our hypothesis with a computational model performing a motor adaptation task and reproduce the behavioral effect of decreased implicit adaptation that appears to be a sign of chronic cannabis use. Finally, we discuss the potential of our hypothesis to explain similar phenomena related to motor impairments following chronic alcohol dependency. © 2022

JTD Keywords: adaptation, addiction, alcohol-abuse, cerebellum, chronic cannabis use, cognition, deficits, endocannabinoid system, error processing, explicit, modulation, motor learning, release, synaptic plasticity, Adaptation, Adaptation, physiological, Alcoholism, Article, Behavioral science, Cannabinoid 1 receptor, Cannabis, Cannabis addiction, Cerebellum, Cerebellum cortex, Cerebellum disease, Chronic cannabis use, Computer model, Down regulation, Endocannabinoid, Endocannabinoid system, Endocannabinoids, Error processing, Hallucinogens, Human, Humans, Motor dysfunction, Motor learning, Nerve cell plasticity, Nonhuman, Physiology, Psychedelic agent, Purkinje-cells, Regulatory mechanism, Sensation, Sensory dysfunction, Sensory error processing impairment, Synaptic transmission, Task performance

Cannabis is the most used illicit substance in the world. As many countries are moving towards decriminalization, it is crucial to determine whether and how cannabis use affects human brain and behavior. The role of the cerebellum in cognition, emotion, learning, and addiction is increasingly recognized. Because of its high density in CB1 receptors, it is expected to be highly affected by cannabis use. The aim of this systematic review is to investigate how cannabis use affects cerebellar structure and function, as well as cerebellar-dependent behavioral tasks. Three databases were searched for peer-reviewed literature published until March 2018. We included studies that focused on cannabis effects on cerebellar structure, function, or cerebellar-dependent behavioral tasks. A total of 348 unique records were screened, and 40 studies were included in the qualitative synthesis. The most consistent findings include (1) increases in cerebellar gray matter volume after chronic cannabis use, (2) alteration of cerebellar resting state activity after acute or chronic use, and (3) deficits in memory, decision making, and associative learning. Age of onset and higher exposure to cannabis use were frequently associated with increased cannabis-induced alterations. Chronic cannabis use is associated with alterations in cerebellar structure and function, as well as with deficits in behavioral paradigms that involve the cerebellum (eg, eyeblink conditioning, memory, and decision making). Future studies should consider tobacco as confounding factor and use standardized methods for assessing cannabis use. Paradigms exploring the functional activity of the cerebellum may prove useful as monitoring tools of cannabis-induced impairment.

JTD Keywords: Behavior, Cannabis use, Cerebellum, Cognitive function, Structure

Background—The cerebellum has been recently suggested as an important player in the addiction brain circuit. Cannabis is one of the most used drugs worldwide, and its long-term effects on the central nervous system are not fully understood. No valid clinical evaluations of cannabis impact on the brain are available today. The cerebellum is expected to be one of the brain structures that are highly affected by prolonged exposure to cannabis, due to its high density in endocannabinoid receptors. We aim to use a motor adaptation paradigm to indirectly assess cerebellar function in chronic cannabis users (CCUs). Methods—We used a visuomotor rotation (VMR) task that probes a putatively-cerebellar implicit motor adaptation process together with the learning and execution of an explicit aiming rule. We conducted a case-control study, recruiting 18 CCUs and 18 age-matched healthy controls. Our main measure was the angular aiming error. Results—Our results show that CCUs have impaired implicit motor adaptation, as they showed a smaller rate of adaptation compared with healthy controls (drift rate: 19.3 +/− 6.8° vs. 27.4 +/− 11.6°; t(26) = −2.1, p = 0.048, Cohen’s d = −0.8, 95% CI = (−1.7, −0.15)). Conclusions—We suggest that a visuomotor rotation task might be the first step towards developing a useful tool for the detection of alterations in implicit learning among cannabis users.

JTD Keywords: Cerebellum, Cannabis, Implicit motor learning, Motor adaptation, Visuomotor rotation

Existing analytical techniques used for the determination of cannabinoids in Cannabis sativa L. (Cannabis) plants mostly rely on chromatography-based methods. As a rapid alternative for the direct analysis of them, thermal desorption (TD)-ion mobility spectrometry (IMS) was used for obtaining spectral fingerprints of single cannabinoids from Cannabis plant extracts and from plant residues on hands after their manipulation. The ionization source was 63Ni, with automatic switchable polarity. Although in both ionization modes there were signals in the TD-IMS spectra of the plant extracts and residues that could be assigned to concrete cannabinoids and chemotypes, most of them could not be clearly distinguished. Alternatively, the global spectral data of the plant extracts and residues were pre-processed and then, using principal component analysis (PCA)-linear discriminant analysis (LDA), grouped in function of their chemotype in a more feasible way. Using this approach, the possibility of false positive responses was also studied analyzing other non-Cannabis plants and tobacco, which were clustered in a different group to those of Cannabis. Therefore, TD-IMS, as analytical tool, and PCA-LDA, as a strategy for data reduction and pattern recognition, can be applied for on-site chemotaxonomic discrimination of Cannabis varieties and detection of illegal marijuana since the IMS equipment is portable and the analysis time is highly short.

JTD Keywords: Cannabis sativa L., Cannabinoids, Chemometrics, ChemotypeIon mobility spectrometry